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Updated: Jun 19, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of
Yuhua Gao1,2, Yanan Zhang3, Ningning Mi4
1Precision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical University, No.133 Hehua Road, Jining, Shandong, 272067, P. R. China.
Background:
Despite increasing evidence supporting the role of an amniotic epithelial-mesenchymal transition (EMT) in the premature rupture of membranes (PROMs), it remains unclear if extracellular vesicle (EV) derived from M1 macrophages play a critical role in triggering the EMT of amniotic epithelial cells (AECs).
Results:
This study revealed that under inflammatory conditions, EV-miR-146a/155 from M1 macrophages could trigger EMTs and MMP-9 transcription in AECs, elevating the risk of PROM in both mice and humans. Introduction of EV-miR-155 led to inhibition of Ehf expression and reduced E-cadherin transcription in AECs. Meanwhile, EV-miR-146a activated the β-catenin/Tcf7 complex to promote the transcription of Snail, MMP-9, and miR-146a/155, inducing EMTs. Subsequently, EMT induction in AECs is associated with a loss of epithelial characteristics, disruption of cellular junctions, widening of intercellular spaces, and diminished biomechanical properties of the amniotic membrane.
Conclusion:
Inflammatory stimulation prompts the polarization of macrophages in amniotic fluid into the M1 type, which subsequently secrete EVs laden with inflammatory miRNAs. These EVs trigger the EMT of AECs, causing the loss of their epithelial phenotype. Consequently, the biomechanical properties of the amnion deteriorate, ultimately leading to its rupture, posing risks relevant to pregnancy complications such as premature rupture of membranes. The results of this study provide insights into the pathogenesis of PROM and will aid in treatment development.
Insights
Extracellular vesicles (EVs) from M1 macrophages carrying specific microRNAs trigger amniotic epithelial cells to undergo transition, weakening the amniotic membrane and increasing the risk of premature rupture of membranes (PROM). This finding offers insights into PROM pathogenesis.
Area of Science:
- Reproductive biology
- Cellular and molecular biology
- Immunology
Background:
- Premature rupture of membranes (PROM) is linked to amniotic epithelial-mesenchymal transition (EMT).
- The role of M1 macrophage-derived extracellular vesicles (EVs) in initiating AEC EMT remains unclear.
Purpose of the Study:
- To investigate if EVs from M1 macrophages trigger EMT in amniotic epithelial cells (AECs).
- To elucidate the molecular mechanisms by which M1 macrophage EVs induce EMT and contribute to PROM.
Main Methods:
- Analysis of EV-miRNA content from M1 macrophages under inflammatory conditions.
- In vitro experiments exposing AECs to M1 macrophage EVs.
- Assessment of EMT markers, gene transcription (MMP-9, E-cadherin, Snail), and protein expression (Ehf, β-catenin/Tcf7).
- Evaluation of changes in cellular morphology and biomechanical properties of the amniotic membrane.
Main Results:
- M1 macrophage EVs containing miR-146a/155 induced EMT and MMP-9 transcription in AECs.
- EV-miR-155 inhibited Ehf and reduced E-cadherin expression.
- EV-miR-146a activated β-catenin/Tcf7, promoting Snail, MMP-9, and miR-146a/155 transcription, thus inducing EMT.
- EMT in AECs led to loss of epithelial characteristics, disrupted junctions, widened intercellular spaces, and reduced membrane biomechanical properties.
Conclusions:
- Inflammatory stimuli polarize macrophages to M1 type, secreting EVs with inflammatory miRNAs.
- These EVs induce AEC EMT, leading to epithelial phenotype loss.
- Deterioration of amnion biomechanics due to EMT increases PROM risk.
- Findings provide insights into PROM pathogenesis and potential therapeutic targets.
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